Pharmacological treatment with annexin A1-derived peptide protects against cisplatin-induced hearing loss.

Cisplatin is an antineoplastic agent widely used, and no effective treatments capable of preventing cisplatin-induced ototoxicity and neurotoxicity in humans have yet been identified. This study evaluated the effect of the anti-inflammatory annexin A1 (AnxA1)-derived peptide Ac2-26 in a cisplatin-induced ototoxicity model. Wistar rats received intraperitoneal injections of cisplatin (10 mg/kg/day) for 3 days to induce hearing loss, and Ac2-26 (1 mg/kg) was administered 15 min before cisplatin administration. Control animals received an equal volume of saline. Hearing thresholds were measured by distortion product otoacoustic emissions (DPOAE) before and after treatments. Pharmacological treatment with Ac2-26 protected against cisplatin-induced hearing loss, as evidenced by DPOAE results showing similar signal-noise ratios between the control and Ac2-26-treated groups. These otoprotective effects of Ac2-26 were associated with an increased number of ganglion neurons compared with the untreated cisplatin group. Additionally, Ac2-26 treatment produced reduced immunoreactivity on cleaved caspase 3 and phosphorylated ERK levels in the ganglion neurons, compared to the untreated group, supporting the neuroprotective effects of the Ac2-26. Our results suggest that Ac2-26 has a substantial otoprotective effect in this cisplatin-induced ototoxicity model mediated by neuroprotection and the regulation of the ERK pathway.

Rosmarinic acid, major phenolic constituent of Greek sage herbal tea, modulates rat intestinal SGLT1 levels with effects on blood glucose.

SCOPE: Previous results suggested that the effects of Salvia fruticosa tea (SFT) drinking on glucose regulation might be at the intestinal level. Here we aim to characterize the effects of SFT treatment and of its main phenolic constituent--rosmarinic acid (RA)--on the levels and localization of the intestinal Na+/glucose cotransporter-1 (SGLT1), the facilitative glucose transporter 2 and glucagon-like peptide-1 (GLP-1). METHODS AND RESULTS: Two models of SGLT1 induction in rats were used: through diabetes induction with streptozotocin (STZ) and through dietary carbohydrate manipulation. Drinking water was replaced with SFT or RA and blood parameters, liver glycogen and the levels of different proteins in enterocytes quantified. Two weeks of SFT treatment stabilized fasting blood glucose levels in STZ-diabetic animals. The increase in SGLT1 localized to the enterocyte brush-border membrane (BBM) induced by STZ treatment was significantly abrogated by treatment with SFT, without significant changes in total cellular transporter protein levels. No effects were observed on glucose transporter 2, Na(+) /K(+) -ATPase or glucagon-like peptide-1 levels by SFT. Additionally, SFT and RA for 4 days significantly inhibited the carbohydrate-induced adaptive increase of SGLT1 in BBM. CONCLUSION: SFT and RA modulate the trafficking of SGLT1 to the BBM and may contribute to the control of plasma glucose.

Ursolic acid and luteolin-7-glucoside improve lipid profiles and increase liver glycogen content through glycogen synthase kinase-3.

In the present study, two phytochemicals - ursolic acid (UA) and luteolin-7-glucoside (L7G) - were assessed in vivo in healthy rats regarding effects on plasma glucose and lipid profile (total cholesterol, HDL and LDL), as well as liver glycogen content, in view of their importance in the aetiology of diabetes and associated complications. Both UA and L7G significantly decreased plasma glucose concentration. UA also significantly increased liver glycogen levels accompanied by phosphorylation of glycogen synthase kinase-3 (GSK3). The increase in glycogen deposition induced by UA (mediated by GSK3) could have contributed to the lower plasma glucose levels observed. Both compounds significantly lowered total plasma cholesterol and low-density lipoprotein levels, and, in addition, UA increased plasma high-density lipoprotein levels. Our results show that UA particularly may be useful in preventable strategies for people at risk of developing diabetes and associated cardiovascular complications by improving plasma glucose levels and lipid profile, as well as by promoting liver glycogen deposition.

Sage tea drinking improves lipid profile and antioxidant defences in humans.

Salvia officinalis (common sage) is a plant with antidiabetic properties. A pilot trial (non-randomized crossover trial) with six healthy female volunteers (aged 40-50) was designed to evaluate the beneficial properties of sage tea consumption on blood glucose regulation, lipid profile and transaminase activity in humans. Effects of sage consumption on erythrocytes' SOD and CAT activities and on Hsp70 expression in lymphocytes were also evaluated. Four weeks sage tea treatment had no effects on plasma glucose. An improvement in lipid profile was observed with lower plasma LDL cholesterol and total cholesterol levels as well as higher plasma HDL cholesterol levels during and two weeks after treatment. Sage tea also increased lymphocyte Hsp70 expression and erythrocyte SOD and CAT activities. No hepatotoxic effects or other adverse effects were observed.

Ocorrência e amplitude do efeito de supressão das emissões otoacústicas evocadas por cliques lineares / Occurence and amplitude of the effect of supression of the otoacoustic emissions evoked by linear clicks

Objetivo: Averiguar a ocorrência e a amplitude de supressão das emissões otoacústicas transitórias (EOAT) em recém-nascidos a termo, sem indicadores de risco para a deficiência auditiva com estímulos cliques lineares e comparar aos cliques não lineares. Material e método: avaliados 19 recém-nascidos com idade entre 30 a 120 dias, que obtiveram EOAT representantes bilateralmente. As EOAT com cliques lineares a 60dB pe NPS(+/-5dB) foram registradas pelo equipamento ILO 96, Otodynamics Analyse, na ausência e presença de ruído branco contralateral a 65dB NPS(+/-5dB). A ocorrência e a amplitude do efeito de supressão foram verificadas comparando-se à variação dos valores da resposta geral, em cada orelha, na presença e ausência do ruído supressor. Resultados: a supressão esteve presente na orelha direita, em 90,0% dos indivíduos do sexo feminino e em 77,8% dos indivíduos do sexo masculino e, na orelha esquerda, em 80,0% dos indivíduos do sexo feminino e em 66,7% dos indivíduos do sexo masculino. A média de amplitude de supressão na orelha direita, foi de 5,17dB para o sexo feminino e de 7,14dB para o sexo masculino e, na orelha esquerda foi de 5,10dB para o sexo feminino e de 6,92dB para o sexo masculino. Não houve diferença estatisticamente significante entre os sexos e orelhas avaliadas quanto à ocorrência e amplitude do efeito de supressão das emissões otoacústicas evocadas por estímulo transiente. Conclusão: a técnica linear, em comparação à não linear, mostrou-se eficaz para a avaliação da função eferente em neonatos a termo, sem fatores de risco para a deficiência auditiva.

Phylogenetic analysis of the order Pleuronectiformes (Teleostei) based on sequences of 12S and 16S mitochondrial genes

The fish order Pleuronectiformes, composed of 14 families, has two suborders: Psettodoidei (with one family) and Pleuronectoidei (with thirteen families). The relationships among families of Pleuronectoidei and among the genera of their families have extensively been debated and a consensus has not yet been reached. In the present study, partial sequences of the 12S and 16S mitochondrial rRNA genes were obtained from 19 species belonging to the families Achiridae, Bothidae, Cynoglossidae, Paralichthyidae, Pleuronectidae, Scophthalmidae, and Soleidae. Additional sequences of 42 pleuronectiform species were obtained from GenBank. Phylogenetic analyses were conducted by the methods of maximum-parsimony, maximum-likelihood and Bayesian inference. Our results corroborate the monophyletic status of all families, excluding Paralichthyidae. In the family Achiridae, the genus Catathyridium (freshwater) was the sister group of Trinectes (saltwater), and Hypoclinemus (freshwater) was the sister group of Achirus (saltwater). Assuming that the putative ancestor of achirids lived in saltwater, it is suggested that the freshwater habitats in South America were colonized independently by different achirid lineages.

Metformin-like effect of Salvia officinalis (common sage): is it useful in diabetes prevention?

Common sage (Salvia officinalis L.) is among the plants that are claimed to be beneficial to diabetic patients, and previous studies have suggested that some of its extracts have hypoglycaemic effects in normal and diabetic animals. In the present study, we aimed to verify the antidiabetic effects of an infusion (tea) of common sage, which is the most common form of this plant consumed. Replacing water with sage tea for 14 d lowered the fasting plasma glucose level in normal mice but had no effect on glucose clearance in response to an intraperitoneal glucose tolerance test. This indicated effects on gluconeogenesis at the level of the liver. Primary cultures of hepatocytes from healthy, sage-tea-drinking rats showed, after stimulation, a high glucose uptake capacity and decreased gluconeogenesis in response to glucagon. Essential oil from sage further increased hepatocyte sensitivity to insulin and inhibited gluconeogenesis. Overall, these effects resemble those of the pharmaceutical drug metformin, a known inhibitor of gluconeogenesis used in the treatment and prevention of type 2 diabetes mellitus. In primary cultures of rat hepatocytes isolated from streptozotocin (STZ)-induced diabetic rats, none of these activities was observed. The present results seem to indicate that sage tea does not possess antidiabetic effects at this level. However, its effects on fasting glucose levels in normal animals and its metformin-like effects on rat hepatocytes suggest that sage may be useful as a food supplement in the prevention of type 2 diabetes mellitus by lowering the plasma glucose of individuals at risk.

Emissöes otoacústicas evocadas transientes (EOAET): amplitude da resposta em recém-nascidos a termo e pré-termo / Transient evoked otoacoustic emissions (TEOAE): response amplitude in term and pre-term neonates

As emissöes otoacústicas evocadas transientes (EOAET) têm sido a técnica mais empregada nas triagens auditivas neonatais. Nos últimos anos, uma análise mais detalhada das EOAET tem evidenciado a presença de características até entäo pouco exploradas do sistema auditivo periférico. OBJETIVO: O objetivo deste trabalho foi o de estudar o comportamento da amplitude de resposta das EOAET em recém-nascidos a termo e pré-termo em funçäo dos parâmetros lados da orelha, sexo, espectro de freqüência e idade pós-concepcional. FORMA DE ESTUDO: Clínico prospectivo. MATERIAL E MÉTODO: A amostra compôs-se de 526 recém-nascidos, sendo 440 nascidos a termo e 86 nascidos pré-termo. Estes últimos foram subdivididos em um grupo com idade pós-concepcional na data do teste variando entre 31 e 36 semanas e outro grupo com idade pós-concepcional na data do teste variando entre 37 e 44 semanas. O teste das EOAET foi realizado em ambiente sem tratamento acústico com o analisador de emissöes otoacústicas ILO 88 da Otodynamics, no modo "Quickscreener". RESULTADO: Ao analisarmos os resultados, observamos assimetria significante da amplitude média de resposta a favor da orelha direita, do sexo feminino, das bandas de freqüências altas e dos recém-nascidos com maior idade pós-concepcional. Estas assimetrias sugerem que o parâmetro amplitude, além de fornecer evidência da presença das EOAET e portanto da integridade do sistema auditivo periférico, também pode ser tomado como um indicador de maturaçäo do sistema auditivo periférico em recém-nascidos

Acompanhamento audiológico em pacientes com osteossarcoma submetidos à quimioterapia com cisplatina / Audiological Follow Up in Patients with Osteosarcoma Who Had Chemotherapy Using Cisplatin

A comunicação humana processa-se por meio da linguagem e da fala, e é através da audição que o homem as adquire e conserva. A deficiência auditiva é considerada doença severamente incapacitante e pode ser causada por diversos fatores, como o uso de ototóxicos. A cisplatina é um antineoplásico, utilizado com bons resultados em diversos tumores, mas apresenta alto grau de toxicidade, causando alterações renais e auditivas. Sendo assim, a monitorização dos limiares de audibilidade, especialmente nas altas freqüências, é importante durante a administração desta droga. A audiometria de altas freqüências tem sido realizada em pacientes tratados com quimioterápicos, possibilitando a detecção de alterações auditivas antes mesmo que as freqüências importantes para a compreensão da fala sejam comprometidas. Objetivo: O objetivo deste estudo foi monitorizar os limiares de audibilidade de pacientes com osteossarcoma, sem tratamento prévio, submetidos à quimioterapia com cisplatina e carboplatina. Material e método: Foram estudados os limiares de audibilidade obtidos em 27 pacientes, nos períodos pré, durante e pós-tratamento quimioterápico. Resultados: A audiometria de altas freqüências identificou mudanças nos limiares de audibilidade em 100% dos casos, na primeira avaliação audiológica realizada durante o tratamento. Em 33,3% dos casos, os limiares permaneceram normais na faixa de freqüências convencional até o término do tratamento; e em 66,6%, alterados. Conclusão: Observamos que na dose de 300 mg/m2 de cisplatina ocorrem mudanças significativas dos limiares de audibilidade, que se mantêm até o término do tratamento quimioterápico, não havendo mudanças significativas nas avaliações subseqüentes. Estes dados sugerem que a avaliação audiológica seja realizada a cada ciclo de administração de cisplatina.

Introduction: Human communication is based on language and speech and hearing plays a definite role in this acquisition process. Hearing loss is-considered as a severe impairment, it can have many etiologies, and ototoxicity is among them. Cisplatin is a chemotherapeutic agent used with success in various tumors. However its high level of toxicity is also known, leading to renal and hearing disorders. Therefore, evaluation of hearing thresholds, specially in high frequency range, is very important during the treatment. High frequency audiometry has been useful in determining hearing disorders before the frequency range for speech is compromised in patients undergoing chemotherapy. Aim: The aim of this study was to evaluate and monitor hearing thresholds of patients with osteosarcoma, without previous treatment, who had undergone chemotherapy using cisplatin and carboplatin. Material and metods: Hearing thresholds of 27 patients, pre, during and post chemotherapy were studied. Results: High frequency audiometry carried out during the treatment has showed changes in hearing thresholds in all cases. Hearing thresholds were within normal limits in conventional frequency range in 33,3% of the cases and 66,6% of patients had altered thresholds by the end of the treatment. Conclusion: We have observed significant changes in hearing thresholds at 300 mg/m2 dose of cisplatin, and these changes were stable throughout the treatment. These findings suggest that hearing evaluation should be performed after each stage of cisplatin administration.

Neuropatia auditiva: relato de caso / Auditory Neuropaty: case report

Este artigo relata um caso de neuropatia auditiva em paciente jovem submetida a intervenção precoce.

This article relates a case of auditory neuropathy in a young patient, who have received early intervention.

Recém-nacidos pré-termo internados em unidade de terapia intensiva: desenvolvimento da conduta interativa no primeiro ano de vida / Preterm neonates treated in intensive care units: development of interaction behavior in the first year of life

Objetivo: Com o presente estudo, pretendemos caracterizar a conduta interativa, no primeiro ano de vida, de recém-nascidos pré-termo, de peso inferior a 2000 gramas, e tempo de internaçäo em unidade neonatal superior a 10 dias. Método: Para tanto, foram observadas 53d crianças, durante o primeiro ano de vida, 21 do sexo masculino e 32 do sexo feminino. As obervaçöes foram realizadas através de 17 comportamentos relacionados à situaçäo de comunicaçäo pessoa-pessoa, ou seja, comportamentos que manifestam desencadeando ou mantendo a situaçäo de interaçäo. Para o estudo estatístico, levou-se em conta as variáveis idade da consulta, sexo, peso ao nascimento, classificaçäo do neonato, tempo de internaçäo e avaliaçäo neurológica. Resultados: Podemos observar que houve evoluçäo nas formas de interaçäo dos recém-nascidos pré-termo, embora com ritmo diferente daquele previsto em crianças nascidas a termo. A ocorrência dos comportamentos comunicativos näo se mostrou afetada pelo sexo, peso ao nascimento e classificaçäo do neonato em adequado ou pequeno à idade gestacional. O tempo de interaçäo afetou a ocorrência do comportamento sorri para a imagem refletida no espelho. As crianças com exame neurológico alterado tiveram uma diminuiçäo estatisticamente significante da ocorrência dos comportamentos sorri para o sorriso e para a fala do examinador, brinca de esconder, protesta para a saída da mäe, aponta para indicar desejo e executa ordens a pedido. Conclusäo: Ficaram caracterizados atrasos na ocorrência de comportamentos que envolviam formas mais complexas, de interaçäo, nas crianças com diagnóstico de alteraçäo neurológica. As crianças com tempo de internaçäo superior a 35 dias mostraram evidência de alteraçäo no processo de construçäo da imagem corporal, processo este relacionado à construçäo da personalidade